Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients

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Abstract

Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNβ-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of ≤3.5 at entry, disability progression at follow-up was defined as EDSS ≥6.0. Two methods were used to estimate the expected proportions that reached EDSS ≥6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNβ-1a patients reached an EDSS ≥6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNβ-1a patients should have reached an EDSS ≥6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNβ-1a group. Treatment effect sizes of 75-90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to vigorously followed cohorts of patients.

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Keywords

  • Disease-modifying drug therapy
  • Interferon beta
  • Multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Rudick, R. A., Cutter, G. R., Baier, M., Weinstock-Guttman, B., Mass, M., Fisher, E., ... Sandrock, A. W. (2005). Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients. Multiple Sclerosis, 11(6), 626-634. https://doi.org/10.1191/1352458505ms1203oa